This Exploratory/Developmental Research (R21) application proposes a new type of imaging microscope that can dramatically increase the application range of optical microscopy and simplify existing biomedicine analysis procedures. This method, termed Optofluidic Microscopy (OFM), operates by flowing the sample over a specially designed array of holes within a microfluidic channel that is illuminated with a uniform light field. The interaction of the object with the illumination field can then by monitored via the transmission through the holes; the shape and refractive index variation of the bioentity can be resolved with a resolution that is limited by the hole size. In addition, the imaging approach employed in this new microscope type implies that high throughput and massively serial/parallel imaging of bioentities is possible. The device will be very compact (about the size of a matchbox), completely free of bulk optics, capable of high throughput processing, and inexpensive. Its fabrication can be done with existing semiconductor chip technology. Among other uses, it can be applied in microfluidic based cell or microorganism analysis, and any other type of lab-on-a-chip applications where a compact and low cost imaging system is desired. Given that imaging on a lab-on-a-chip system is generally performed with a bulky microscope at present, the OFM will enable the creation of truly compact lab-on-a-chip systems. We have already demonstrated a working device that is capable of high throughput imaging with resolution of 0.6 microns. The fabrication technology employed in our preliminary studies is readily scalable and we are confident that, with the right resources, we can fully demonstrate the utility, low cost to mass produce, and associated advantages of the OFM. To evaluate OFM's utility for biomedical applications, we will apply the OFM to address a specific biomedical application - C. elegans phenotyping. With the completion of the proposed research, we expect the technology will be sufficiently refined to tackle a wide range of basic research and biomedicine challenges. [unreadable] [unreadable] [unreadable]